RESUMO
OBJECTIVE: To investigate the frequency of occurrence of polycystic ovaries (PCO) in women taking valproic acid (VPA) as monotherapy for epilepsy. STUDY DESIGN AND PATIENTS: 163 epileptic patients were seen at the outpatient neurology clinic at Princess's Basma Teaching Hospital, Irbid, and Basheer Hospital, Amman, Jordan. A detailed medical history was taken from the patients followed by a clinical examination and vaginal ultrasonography of the ovaries. RESULTS: 102 patients (62.5%) had primary generalised seizures, 46 patients (28.2%) had partial seizures and 15 patients (9.2%) had partial secondary generalised seizures. Mean age +/- standard error of the mean (SEM) was 29.8 +/- 0.97 years. The duration of epilepsy and treatment with VPA were (mean +/- SD) 9.1 +/- 0.48 and 7.9 +/- 0.4 years, respectively. The dose and serum concentrations of VPA were (mean +/- SD) 983.9 +/- 101.96mg and 52.7 +/- 4.7 mg/L, respectively. Mean body mass index (BMI) was 25.6 +/- 0.92 kg/m(2). The mean weight gain was 6.6 +/- 1.3kg (range 2-24kg). Menstrual abnormalities were detected in 58 (35.6%) patients. Twelve patients (7.4%) had PCO; these patients were compared with 17 patients without PCO selected randomly. There was a statistically significant difference in testosterone level and BMI values in patients with PCO compared with those without negative PCO. Patients with PCO had a mean +/- SEM serum testosterone level of 1.2 +/- 0.18 mug/L and BMI values of 29.24 +/- 1.75 kg/m(2). However, patients without PCO had a serum testosterone level of 0.61 +/- 0.1 mug/L and a BMI of 21.91 +/- 0.7 kg/m(2). Menstrual abnormalities were detected in all patients with PCO and in eight patients without PCO. Hirsutism was found in four cases with PCO and in one case with no PCO. There were no statistically significant differences in the duration of therapy, doses and serum concentrations of VPA in patients with PCO compared with those without PCO. CONCLUSION: These results suggest an association between the use of VPA and PCO, hyperandrogenism, obesity and menstrual abnormalities. For women receiving VPA therapy, clinicians should consider performing an assessment of ovarian structure and function, especially if these patients develop menstrual cycle disturbances during treatment.
RESUMO
Infection of C57BL/6 mice with mouse hepatitis virus (MHV) results in a demyelinating encephalomyelitis characterized by mononuclear cell infiltration and white matter destruction similar to the pathology of the human demyelinating disease multiple sclerosis. The contributions of CD4(+) and CD8(+) T cells in the pathogenesis of the disease were investigated. Significantly less severe inflammation and demyelination were observed in CD4(-/-) mice than in CD8(-/-) and C57BL/6 mice (P < or = 0.002 and P < or = 0.001, respectively). Immunophenotyping of central nervous system (CNS) infiltrates revealed that CD4(-/-) mice had a significant reduction in numbers of activated macrophages/microglial cells in the brain compared to the numbers in CD8(-/-) and C57BL/6 mice, indicating a role for these cells in myelin destruction. Furthermore, CD4(-/-) mice displayed lower levels of RANTES (a C-C chemokine) mRNA transcripts and protein, suggesting a role for this molecule in the pathogenesis of MHV-induced neurologic disease. Administration of RANTES antisera to MHV-infected C57BL/6 mice resulted in a significant reduction in macrophage infiltration and demyelination (P < or = 0.001) compared to those in control mice. These data indicate that CD4(+) T cells have a pivotal role in accelerating CNS inflammation and demyelination within infected mice, possibly by regulating RANTES expression, which in turn coordinates the trafficking of macrophages into the CNS, leading to myelin destruction.
